PUBLICATION
The Thyroid Hormone Inactivating Type 3 Deiodinase is Essential for Optimal Neutrophil Function - observations from 3 species
- Authors
- van der Spek, A.H., Jim, K.K., Karaczyn, A., van Beeren, H.C., Ackermans, M.T., Darras, V.M., Vandenbroucke-Grauls, C.M.J.E., Hernandez, A., Brouwer, M.C., Fliers, E., van de Beek, D., Boelen, A.
- ID
- ZDB-PUB-171204-24
- Date
- 2017
- Source
- Endocrinology 159(2): 826-835 (Journal)
- Registered Authors
- Darras, Veerle
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Case-Control Studies
- Cells, Cultured
- Embryo, Nonmammalian
- Iodide Peroxidase/genetics
- Iodide Peroxidase/physiology*
- Meningitis, Bacterial/cerebrospinal fluid
- Meningitis, Bacterial/immunology
- Mice, Knockout
- Neutrophils/physiology*
- Species Specificity
- Thyroid Hormones/cerebrospinal fluid
- Thyroid Hormones/metabolism
- Triiodothyronine, Reverse/cerebrospinal fluid
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 29186449 Full text @ Endocrinology
Citation
van der Spek, A.H., Jim, K.K., Karaczyn, A., van Beeren, H.C., Ackermans, M.T., Darras, V.M., Vandenbroucke-Grauls, C.M.J.E., Hernandez, A., Brouwer, M.C., Fliers, E., van de Beek, D., Boelen, A. (2017) The Thyroid Hormone Inactivating Type 3 Deiodinase is Essential for Optimal Neutrophil Function - observations from 3 species. Endocrinology. 159(2):826-835.
Abstract
Neutrophils are essential effector cells of the innate immune system that have recently been recognized as thyroid hormone (TH) target cells. Cellular TH bioavailability is regulated by the deiodinase enzymes, which can activate or inactivate TH. We have previously shown that the TH inactivating enzyme type 3 deiodinase (D3) is present in neutrophils. Furthermore, D3KO mice show impaired bacterial killing upon infection. We hypothesized that D3 plays a role in neutrophil function during infection by actively regulating local TH availability.We measured TH concentrations in cerebrospinal fluid (CSF) from patients with bacterial meningitis and controls. Bacterial meningitis resulted in marked changes in CSF TH levels, characterized by a strong increase of thyroxine and reverse-triiodothyronine concentrations. This altered TH profile was consistent with elevated D3 activity in infiltrating neutrophils at the site of infection. D3 knockdown in zebrafish embryos with pneumococcal meningitis resulted in increased mortality and reduced neutrophil infiltration during infection. Finally, stimulated neutrophils from female D3KO mice exhibited impaired NADPH-oxidase activity, an important component of the neutrophil bacterial killing machinery.These consistent findings across experimental models strongly support a critical role for reduced intracellular TH concentrations in neutrophil function during infection, for which the TH inactivating enzyme D3 appears essential.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping